Cartilage regeneration

Formation of chondromimetic human mesenchymal stem cells (hMSCs) condensations typically required in vitro culture in defined environments. In addition, extended in vitro culture in differentiation media over several weeks is usually necessary prior to implantation, which is costly, time consuming and delays clinical treatment. Here, this study reports on immediately implantable core/shell microgels with a high-density hMSC-laden core and rapidly degradable hydrogel shell. The hMSCs in the core formed cell condensates within 12 hours and the oxidized and methacrylated alginate (OMA) hydrogel shells were completely degraded within 3 days, enabling spontaneous and precipitous fusion of adjacent condensed aggregates...

The prevalence of articular cartilage injuries and osteoarthritis (OA) is high, affecting a wide range of individuals. The self-repair ability of cartilage tissue is poor, and once damaged, it will irreversibly progress to OA. Mesenchymal stem cells (MSCs) play an important role in the field of regenerative medicine and are considered one of the most promising seed cells for cartilage repair and regeneration. In this article, based on the latest clinical research findings from both domestic and international sources, the theoretical basis, treatment goals, significance, sources, characteristics, clinical implementation plans, and efficacy of using MSCs for the treatment of cartilage injuries or osteoarthritis are reviewed...

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously...

Enhancing the regeneration of cartilage defects remains challenging owing to limited innate self-healing as well as acute inflammation arising from the overexpression of reactive oxygen species (ROS) in post-traumatic microenvironments. Recently, stem cell-derived exosomes (Exos) have been developed as potential cell-free therapy for cartilage regeneration. Although this approach promotes chondrogenesis, it neglects the emerging inflammatory microenvironment. In this study, a smart bilayer-hydrogel dual-loaded with sodium diclofenac (DC), an anti-inflammatory drug, and Exos from bone marrow-derived mesenchymal stem cells was developed to mitigate initial-stage inflammation and promote late-stage stem-cell recruitment and chondrogenic differentiation...

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process...

Degradable rotator cuff patches, followed over five years, have been observed to exhibit high re-tear rates exceeding 50%, which is attributed to the inability of degradable polymers alone to restore the post-rotator cuff tear (RCT) inflammatory niche. Herein, poly(ester-ferulic acid-urethane)urea (PEFUU) was developed, featuring prolonged anti-inflammatory functionality, achieved by the integration of ferulic acid (FA) into the polyurethane repeating units. PEFUU stably releases FA in vitro, reversing the inflammatory niche produced by M1 macrophages and restoring the directed differentiation of stem cells...

Osteochondral tissue (OC) repair remains a significant challenge in the field of musculoskeletal tissue engineering. OC tissue displays a gradient structure characterised by variations in both cell types and extracellular matrix components from cartilage to the subchondral bone. These functional gradients in the native tissue have been replicated to engineer osteochondral tissue in vitro. While diverse fabrication methods have been employed to create these microenvironments, emulating the natural gradients and effective regeneration of the tissue continues to present a significant challenge...

Bone development, growth, and repair are complex processes involving various cell types and interactions, with central roles played by skeletal stem and progenitor cells. Recent research brought new insights into the skeletal precursor populations that mediate intramembranous and endochondral bone development. Later in life, many of the cellular and molecular mechanisms determining development are reactivated upon fracture, with powerful trauma-induced signaling cues triggering a variety of postnatal skeletal stem/progenitor cells (SSPCs) residing near the bone defect...

Osteoarthritis (OA) is distinguished by pathological alterations in the synovial membrane, articular cartilage, and subchondral bone, resulting in physical symptoms such as pain, deformity, and impaired mobility. Numerous research studies have validated the effectiveness of low-intensity pulsed ultrasound (LIPUS) in OA treatment. The periodic mechanical waves generated by LIPUS can mitigate cellular ischemia and hypoxia, induce vibration and collision, produce notable thermal and non-thermal effects, alter cellular metabolism, expedite tissue repair, improve nutrient delivery, and accelerate the healing process of damaged tissues...

Tissue defect is one of the significant challenges encountered in clinical practice. Nanomaterials, including nanoparticles, nanofibers, and metal-organic frameworks, have demonstrated an extensive potential in tissue regeneration, offering a promising avenue for future clinical applications. Nonetheless, the intricate landscape of the inflammatory tissue microenvironment has engendered challenges to the efficacy of nanomaterial-based therapies. This quandary has spurred researchers to pivot towards advanced nanotechnological remedies for overcoming these therapeutic constraints...

Silk fibroin, extracted from the silk of the Bombyx mori silkworm, stands out as a biomaterial due to its nontoxic nature, excellent biocompatibility, and adjustable biodegradability. Porous scaffolds, a type of biomaterial, are crucial for creating an optimal microenvironment that supports cell adhesion and proliferation, thereby playing an essential role in tissue remodeling and repair. Therefore, this review focuses on 3D porous silk fibroin-based scaffolds, first summarizing their preparation methods and then detailing their regenerative effects on bone, cartilage, tendon, vascular, neural, skin, hepatic, and tracheal epithelial tissue engineering in recent years...

Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy. Definitive treatment ultimately requires joint replacement. Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs. The regenerative potential of mesenchymal stromal cells (MSCs) has been extensively studied in the context of knee osteoarthritis. This has yielded promising results in human studies, and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation...

The reconstruction of a stable, nipple-shaped cartilage graft that precisely matches the natural nipple in shape and size on the contralateral side is a clinical challenge. While 3D printing technology can efficiently and accurately manufacture customized complex structures, it faces limitations due to inadequate blood supply, which hampers the stability of nipple-shaped cartilage grafts produced using this technology. To address this issue, we employed a biodegradable biomaterial, Poly(lactic-co-glycolic acid) (PLGA), loaded with Cell-Free Fat Extract (Ceffe)...

PURPOSE: The retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. METHODS: Thirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively...

Hydrogels containing chondrocytes have exhibited excellent potential in regenerating hyaline cartilage. However, chondrocytes are vulnerable to dedifferentiation during in vitro culture, leading to fibrosis and mechanical degradation of newly formed cartilage. We propose to modulate cartilage formation via the developed chondrocyte pericellular matrix (PCM) -like scaffolds for the first time, in which the S, M and L-sized scaffolds were fabricated by femtosecond laser maskless optical projection lithography of bovine serum albumin-glyceryl methacrylate hydrogel...

Tissue engineered scaffolds are needed to support physiological loads and emulate the micrometer-scale strain gradients within tissues that guide cell mechanobiological responses. We designed and fabricated micro-truss structures to possess spatially varying geometry and controlled stiffness gradients. Using a custom projection microstereolithography (μSLA) system, using digital light projection (DLP), and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) hydrogel monomers, three designs with feature sizes < 200 μm were formed: (1) uniform structure with 1 MPa structural modulus ( <mml:math xmlns:mml="https://www...

Intra-articular injection of drugs is an effective strategy for osteoarthritis (OA) treatment. However, the complex microenvironment and limited joint space result in rapid clearance of drugs. Herein, a nanogel-based strategy was proposed for prolonged drug delivery and microenvironment remodeling. Nanogel was constructed through functionalization of hyaluronic acid (HA) by amide reaction on the surface of Kartogenin (KGN)-loaded zeolitic imidazolate framework-8 (denoted as KZIF@HA). Leveraging the inherent hydrophilicity of HA, KZIF@HA spontaneously forms nanogels, ensuring extended drug release in the OA microenvironment...

Epidemiological studies reveal that symptoms of temporomandibular joint disorders (TMDs) occur in 60-70% of adults. The inflammatory damage caused by TMDs can easily lead to defects in the articular disc, condylar cartilage, subchondral bone and muscle of the temporomandibular joint (TMJ) and cause pain. Despite the availability of various methods for treating TMDs, few existing treatment schemes can achieve permanent recovery. This necessity drives the search for new approaches. Hydrogels, polymers with high water content, have found widespread use in tissue engineering and regeneration due to their excellent biocompatibility and mechanical properties, which resemble those of human tissues...

Osteochondral lesion of the talus (OLT) is a commune cause of chronic ankle pain. Symptomatic lesions require surgical treatment. Currently, lesions with diameter less than 107.4 mm2  are treated with bone marrow stimulating technique with notable success rate. However, more extensive lesions show less predictable surgical results. Autologous matrix-induced chondrogenesis has proven to provide satisfactory medium and long-term results on OLTs. In the current review, we describe an all-arthroscopic technique and the Milan-Tel Aviv lesion assessment protocol...

Bone Marrow Stimulation of osteochondral lesions of the talus has been shown to be a successful way to treat cartilage injuries. Newer data suggest that Bone Marrow Stimulation is best reserved for osteochondral lesions of the talus Sizes Less Than 107.4 mm2 in area. Additionally, newer smaller and deeper techniques to perform bone marrow stimulation have resulted in less subchondral bone damage, less cancellous compaction, and superior bone marrow access with multiple trabecular access channels. Biologic adjuvants such as platelet-rich plasma (PRP), hyaluronic acid (HA), and bone marrow aspirate concentrate (BMAC) may lead to better functional outcomes when used concomitant to bone marrow stimulation...